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Early myeloid cell infiltration and subset-specific macrophage responses in murine corneal nerve injury 小鼠角膜神经损伤的早期髓样细胞浸润和亚群特异性巨噬细胞反应
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-07-10 DOI: 10.1016/j.jtos.2025.07.001
Seung Hyeun Lee , Soo Jin Lee , Ahra Koh , Yunjin Lee , Seonghan Kim , Suil Jeon , Noseong Park , Chang Ho Yoon , Ki Hean Kim , Kyoung Woo Kim

Purpose

Corneal nerve fibers and resident macrophages form a specialized microenvironment essential for tissue integrity and recovery after injury. This study aims to elucidate the early immune dynamics following corneal nerve injury, focusing on myeloid cell infiltration and resident macrophage subset shifts.

Methods

Using a murine circular nerve-cut model, we tracked immune responses for 21 days, with a focus on the first 12 h post-injury. Confocal imaging was used to assess corneal nerve density, while flow cytometry quantified infiltrating and resident immune cell populations. Transcriptomic profiling was performed at 3 and 6 h post-injury to analyze inflammatory gene expression, and in vitro experiments examined the effects of short-term nerve growth factor (NGF) exposure on macrophage polarization.

Results

Confocal imaging showed a rapid decrease in corneal nerve density, followed by progressive regeneration. Flow cytometry revealed a surge in Ly6C+ myeloid cells at 3–6 h post-injury, predominantly in the central cornea, with an early tendency toward M2-like polarization. Resident macrophages exhibited distinct responses: M2-like and undifferentiated subsets declined, while M1-like cells were proportionally maintained, indicating divergent but complementary roles during the initial inflammatory phase. Transcriptomic profiling showed significant upregulation of inflammatory genes along with a transient increase in Ngf and compensatory anti-inflammatory signaling. In vitro, short-term NGF exposure enhanced both M1-and M2-like polarization, mirroring in vivo activation patterns.

Conclusion

Early myeloid cell infiltration and macrophage subset dynamics contribute to the initial neuroinflammatory response and may influence subsequent repair processes, highlighting the potential for immune modulation in corneal nerve regeneration.
角膜神经纤维和常驻巨噬细胞形成了一个特殊的微环境,对损伤后组织的完整性和恢复至关重要。本研究旨在阐明角膜神经损伤后的早期免疫动力学,重点关注骨髓细胞浸润和常驻巨噬细胞亚群转移。
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引用次数: 0
Specificity of direct immunofluorescence in healthy conjunctival specimens 直接免疫荧光在健康结膜标本中的特异性。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-25 DOI: 10.1016/j.jtos.2025.06.003
Anahita Kate , Poornima Golthi , Swapna S. Shanbhag , Megana Peddi , Simmy Chaudhary , Saumya Jakati , Sayan Basu
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引用次数: 0
Moxifloxacin-resistant and moxifloxacin-susceptible Staphylococcus aureus Keratitis: Outcomes from a 10-year retrospective study 莫西沙星耐药和莫西沙星敏感的金黄色葡萄球菌角膜炎:10年回顾性研究的结果
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-23 DOI: 10.1016/j.jtos.2025.06.008
Raven Diacou , Rohan Bir Singh , Eric G. Romanowski , Jonathan B. Mandell , Alex Mammen , Robert M.Q. Shanks , Vishal Jhanji

Purpose

Fluoroquinolones, specifically moxifloxacin are commonly used to treat bacterial keratitis. However, recent clinical evidence assessing the clinical outcomes in bacterial keratitis cases resistant to moxifloxacin remains sparse. This study evaluates the clinical characteristics and outcomes in cases of Staphylococcus aureus keratitis with in vitro resistance to moxifloxacin.

Design

Retrospective clinical cohort study.

Methods

Keratitis patients with cultures positive for Staphylococcus aureus at the University of Pittsburgh Medical Center, were identified between July 2012 and June 2022.

Results

A total of 104 patients with culture-confirmed Staphylococcus aureus keratitis were included in the study. Patients infected by moxifloxacin-resistant bacteria (n = 32) were significantly older (74.32 ± 17.41 years) than moxifloxacin-susceptible infections (55.56 ± 20.86 years, p < 0.0001). Moxifloxacin resistance was identified in 29.8 % of cases, including methicillin-susceptible (4.8 %) and methicillin-resistant Staphylococcus aureus (25.96 %) isolates. The most common risk factors for moxifloxacin resistance were ocular surface disease (35.5 %) and history of prior infection (32.2 %). Moxifloxacin-resistant Staphylococcus aureus was associated with larger epithelial defects (18.18 ± 4.93 mm2 vs. 5.10 ± 0.76 mm2, p < 0.0001), longer healing times (42.42 ± 6.75 days vs. 32.2 ± 3.56 days, p < 0.0001), and higher rates of corneal perforation (19.3 % vs. 4.2 %; p = 0.0317). Visual acuity outcomes were significantly worse in the resistant group, with minimal improvement from baseline (1.87 ± 0.14 LogMAR) to final follow-up (1.8 ± 0.18 LogMAR), compared to the moxifloxacin-susceptible group (from 1.46 ± 0.11 LogMAR to 1.15 ± 0.11 LogMAR, p < 0.0001). Enucleation was required in 9.6 % of resistant cases.

Conclusions

The current study determined significant differences in clinical characteristics and outcomes among corneal ulcers caused by moxifloxacin-resistant Staphylococcus aureus.
目的氟喹诺酮类药物,特别是莫西沙星常用于治疗细菌性角膜炎。然而,最近评估细菌性角膜炎对莫西沙星耐药的临床结果的临床证据仍然很少。本研究对莫西沙星体外耐药金黄色葡萄球菌角膜炎的临床特点和预后进行了评价。设计回顾性临床队列研究。方法选取2012年7月至2022年6月在匹兹堡大学医学中心发现的金黄色葡萄球菌培养阳性的角膜炎患者。结果共纳入104例经培养证实的金黄色葡萄球菌角膜炎患者。莫西沙星耐药菌感染患者(n = 32)年龄(74.32±17.41岁)明显大于莫西沙星敏感菌感染患者(55.56±20.86岁,p <;0.0001)。29.8%的病例耐莫西沙星,其中甲氧西林敏感(4.8%)和耐甲氧西林金黄色葡萄球菌(25.96%)。莫西沙星耐药最常见的危险因素是眼表疾病(35.5%)和既往感染史(32.2%)。耐莫西沙星金黄色葡萄球菌与较大的上皮缺损相关(18.18±4.93 mm2 vs. 5.10±0.76 mm2, p <;0.0001),较长的愈合时间(42.42±6.75天vs. 32.2±3.56天,p <;0.0001),角膜穿孔率较高(19.3% vs. 4.2%;p = 0.0317)。与莫西沙星敏感组(从1.46±0.11 LogMAR到1.15±0.11 LogMAR)相比,耐药组的视力结果明显更差,从基线(1.87±0.14 LogMAR)到最终随访(1.8±0.18 LogMAR)的改善极小(p <;0.0001)。9.6%的耐药病例需要去核。结论本研究确定了耐莫西沙星金黄色葡萄球菌引起的角膜溃疡的临床特征和结局存在显著差异。
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引用次数: 0
Corrigendum to “Models for Meibomian gland dysfunction: In vivo and in vitro”, Review article [Ocul. Surf. 32 (2024) 154–165] “睑板腺功能障碍模型:体内和体外”的勘误表。综述文章,眼表32(2024)154-165。
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-23 DOI: 10.1016/j.jtos.2025.06.009
Jinghua Bu , Yuli Guo , Yang Wu , Rongrong Zhang , Jingbin Zhuang , Jiankai Zhao , Le Sun , Andrew J. Quantock , Zuguo Liu , Wei Li
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引用次数: 0
Ultrasonography assessments of meibomian gland as a noninvasive method of detecting changes in morphology 超声评估睑板腺作为一种无创检测形态学变化的方法
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-20 DOI: 10.1016/j.jtos.2025.06.006
Liyun Wang , Hongbo Yin , Yujia Yang , Li Qiu

Purpose

We employed 24 MHz ultrasonography to evaluate the morphological features of meibomian glands (MGs) and compared the ultrasonic differences in morphology between healthy volunteers and meibomian gland dysfunction (MGD) patients.

Methods

24 MHz ultrasound examinations on both the upper and lower eyelids of healthy volunteers and patients with MGD, using transverse and longitudinal sections. The reproducibility of ultrasonographic findings for the MG was evaluated, and a comparison of morphological characteristics at different examination sites between the two groups was made.

Results

Among 89 participants, 24 were healthy volunteers and 65 had MGD. The cross-sectional ultrasound findings showed well-organized punctate hyperechoic ducts within the tarsal plate, surrounded by hypoechoic acinar formations, which were further classified based on the extent of MG involvement into three categories: normal, ≤50 % involvement, and >50 % involvement. Additionally, a typical longitudinal ultrasound appearance of a MG consisted of a thin band-like hypoechoic structure (acinar) with uniform thickness accompanied by an arc-shaped linear hyperechoic duct in its middle region. Furthermore, seven abnormal longitudinal ultrasound manifestations were categorized as distortion, ectasia, central duct truncation, cyst formation, structureless appearance, complete disappearance or other findings. The intra- and inter-observer agreement for those categories was found to be high (ICC>0.6). MGD patients exhibited a higher likelihood of overall MG involvement or abnormal ultrasound findings, particularly in relation to the middle part of the upper eyelid.

Conclusion

The present study has developed an initial classification method to identify abnormalities in MG morphology using 24 MHz ultrasound in MGD patients.
采用24 MHz超声对睑板腺(mg)的形态学特征进行了评价,并比较了健康志愿者与睑板腺功能障碍(MGD)患者的超声形态学差异。
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引用次数: 0
Ocular surface epithelial immune cells and corneal nerves in dry eye disease - A systematic review and meta-analysis of in vivo confocal microscopy data 干眼病的眼表上皮免疫细胞和角膜神经-体内共聚焦显微镜数据的系统回顾和荟萃分析
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-20 DOI: 10.1016/j.jtos.2025.06.005
Soumen Sadhu , Isabelle Jalbert , Luz Palacios-Derflingher , Ali Alghamdi , Blanka Golebiowski , Fiona Stapleton

Purpose

To examine ocular surface epithelial immune cell (EIC) density and corneal nerve parameters between patients with dry eye disease (DED) compared to healthy controls with further comparisons between auto-immune - Sjӧgren Syndrome DED (SS-DED) and non-autoimmune – non-Sjӧgren Syndrome DED (NSS-DED) subtypes.

Methods

A systematic review and meta-analysis following PRISMA guidelines (Prospero-CRD42023446763) were conducted including studies reporting corneal and conjunctival EIC density and/or corneal nerve parameters in DED and healthy controls using in vivo confocal microscopy. Electronic databases – PubMed, Embase, Scopus, Web of Science were searched from inception to March 2025.

Results

The meta-analysis included 24 studies (n = 1060 DED, n = 521 controls) reporting EIC density, 30 studies reporting nerve length (CNL; n = 1450 DED, n = 643 controls) and 20 studies reporting nerve density (CND; n = 919 DED, n = 462 controls) in the central cornea. Studies of other ocular surface locations were insufficient for meta-analysis. Higher central corneal EIC density was evident in DED compared to controls (MD: 57.9 cells/mm2; 95 % CI: 43.3, 72.5; p < 0.001), and in, SS-DED compared to NSS-DED (51.0 cells/mm2; 95 % CI: 12.0, 90.0; p = 0.01). DED had lower CNL (−4.0 mm/mm2; 95 % CI: 5.2, −2.7; p < 0.001) and CND (−7.2 nerves/mm2; 95 % CI: 10.3, −4.1; p < 0.001) compared to controls. No significant differences in nerve parameters were found between SS-DED and NSS-DED subtypes (CNL: 95 % CI: 3.0, 1.4, CND: 6.8, 4.8; p ≥ 0.46).

Conclusion

DED involves substantial EIC infiltration and reduced corneal nerve parameters. SS-DED is distinguished by higher EIC density than NSS-DED, while no differences were observed in corneal nerve parameters.
研究干眼病(DED)患者与健康对照组相比眼表面上皮免疫细胞(EIC)密度和角膜神经参数,并进一步比较自身免疫-Sjӧgren综合征DED (SS-DED)和非自身免疫- non-Sjӧgren综合征DED (NSS-DED)亚型之间的差异。
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引用次数: 0
Heightened visual light sensitivity discomfort measured by the ocular photosensitivity analyzer is associated with chronic ocular pain 眼光敏度分析仪测量的视光敏度升高的不适与慢性眼痛有关
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-19 DOI: 10.1016/j.jtos.2025.06.007
Ema V. Karakoleva , Nicholas Pondelis , Cameron Talbert , Mariela C. Aguilar , Alex Gonzalez , Cornelis Rowaan , Heather Durkee , Paula A. Sepulveda-Beltran , David Valdes-Arias , Chloe Shields , Shreya Bhatt , David Zurakowski , Deborah S. Jacobs , Joseph B. Ciolino , Elizabeth R. Felix , Jean-Marie Parel , Eric A. Moulton , Anat Galor

Purpose

To quantify visual photosensitivity discomfort thresholds (VPDT) in individuals with chronic ocular pain (COP) compared to controls without COP and explore relationships between VPDT, demographics, clinical factors, and ocular metrics.

Methods

Prospective case-control study of 75 participants: 36 with COP (age 46.5 ± 15.6 years; 56 % female) and 39 controls (39.2 ± 15.6 years; 56 % female). COP was defined by self-reported ocular pain intensity ≥15 on a numerical rating scale (range, 0–100) for ≥3 months. COP cases were subclassified into inflammatory (Sjögren's disease) and neuropathic ocular pain subgroups. VPDT was measured using the Ocular Photosensitivity Analyzer (OPA), and ocular symptoms were assessed using the Visual Light Sensitivity Questionnaire (VLSQ-8; 8–40) and Ocular Surface Disease Index (OSDI; 0–100), with OSDI Question 1 addressing light sensitivity (OSDI-Q1; 0–4).

Results

COP patients exhibited lower VPDT than controls (log lux, 1.60 ± 1.17 vs. 2.42 ± 1.05; P = 0.006), indicating greater photosensitivity discomfort. No differences in VPDT were seen across COP subtypes. COP patients also reported greater symptom severity than controls, with higher VLSQ-8 (21.92 ± 1.41 vs. 9.03 ± 0.53), OSDI (50.84 ± 3.88 vs. 2.82 ± 0.85), and OSDI-Q1 (2.00 ± 0.24 vs. 0.14 ± 0.06) scores (all P < 0.001). VPDT negatively correlated with VLSQ-8 (ρ = −0.75) and OSDI-Q1 (ρ = −0.62), demonstrating alignment between subjective light sensitivity symptoms and OPA-measured photosensitivity discomfort. Multivariable regression identified fibromyalgia as the strongest predictor of VPDT (19.6 % variance explained), with chronic fatigue improving the model (26.5 %).

Conclusion

COP subjects display greater photosensitivity-related discomfort than controls, highlighting the OPA's potential as a psychophysical tool for quantifying photoallodynia. Further research is needed to assess its diagnostic utility across COP subtypes.
量化慢性眼痛(COP)患者的视觉光敏性不适阈值(VPDT),并与无COP的对照组进行比较,探讨VPDT、人口统计学、临床因素和眼部指标之间的关系。
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引用次数: 0
Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis 史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症的因果关系归因
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-18 DOI: 10.1016/j.jtos.2025.06.004
Asha Parvathaneni , Liliya Benchetrit , Derek Metcalfe , James T. Kwan , Yandong Bian , Tavé Van Zyl , Hajirah N. Saeed , James Chodosh
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.
史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)是一种急性、严重的皮肤和粘膜免疫大泡性疾病,最常由药物暴露引起。SJS/TEN的病因通常由“表皮坏死松解药物因果关系算法”(ALDEN)工具确定。然而,人们仍然关注ALDEN的准确性和因果关系评估工具,这可能会影响正在进行的试图将特定基因型与特定药物类别作为病因联系起来的研究。为了确定在SJS/TEN的因果归因中是否存在谨慎标准,我们对SJS/TEN的因果关系的当前概念以及用于归因的现有临床和实验室评估工具进行了叙述性回顾。我们发现目前的SJS/TEN因果归因工具,包括ALDEN,在某种程度上受到潜在假设的限制。用于确定SJS/TEN病因的离体试验,特别是淋巴细胞转化试验和细胞因子刺激试验,仍在研究中,要么不适用于急性SJS/TEN,要么尚未得到验证。总之,在SJS/TEN患者的护理中存在一个关键的未满足需求,即难以确定任何特定个体的确切病因。这一缺陷限制了临床医生在急性期仅停用致病因子的能力,混淆了发病机制的研究,并使受影响的患者处于慢性期,而不知道将来使用哪种药物或药物类别是安全的。需要进一步的研究来缩小这一毁灭性疾病护理方面的这一重大差距。
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引用次数: 0
A pilot randomized controlled trial of topical androgen treatment in dry eye 局部雄激素治疗干眼症的随机对照试验
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-14 DOI: 10.1016/j.jtos.2025.06.002
Jay Ruzhang Jiang , Rima Khankan , William H. Ridder III , Andrew Loc Nguyen , Jerry R. Paugh

Purpose

To evaluate the safety and efficacy of eyelid androgen gel application to treat moderate to severe dry eye disease.

Methods

Twenty four eyes of 24 subjects (12 eyes per arm) were randomized to either eyelid testosterone or vehicle gel. Subjects received either 17β-Hydroxyandrost-4-en-3-one) 4.5 % wt./wt. or vehicle gel, applied twice daily 12 h apart for 4 weeks. Outcome parameters were monitored at 2-, and 4-weeks during dosing, and at 4-, and 8-weeks following dosing cessation.

Results

Significant positive differences were found in the androgen arm only, for Schein symptom score, tear meniscus height (TMH), fluorescein tear breakup time (fTBUT) and meibum score (repeated ANOVA, all p = 0.046 or less for each arm comparison) at all follow-up visits compared to baseline. For example, fTBUT in the androgen arm at 4 weeks was 6.2 ± 1.5 s compared to baseline, 3.3 ± 0.9 secs p< 0.001 (Dunnett's test, 95 % CI [1.838, 3.829]). No change was observed for either arm for staining, tear osmolarity, OSDI, non-invasive breakup time (NIBUT), serum lipid levels or hematocrit. Serum testosterone increased ∼ 9-fold in females (paired t-test; p = 0.006; CI [-240.2, −55.6]) in the androgen arm, but not males (paired t-test; p = 0.727; CI [-25.9, 31.2]).

Conclusions

Eyelid androgen gel application, 4.5 % wt./wt., was effective in improving tear fTBUT, symptoms, TMH and meibomian secretion grade in dry eye patients. Future research requires a larger sample size, outcome measure variability reduction and formulation optimization for absorption, androgen type, and dosing regimen.
目的评价眼睑雄激素凝胶治疗中重度干眼病的安全性和有效性。
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引用次数: 0
Association of tobacco smoking with aqueous deficient and evaporative dry eye disease subtypes: a prospective registry-based case-control study 吸烟与水分缺乏性和蒸发性干眼病亚型的关系:一项前瞻性登记病例对照研究
IF 5.9 1区 医学 Q1 OPHTHALMOLOGY Pub Date : 2025-06-13 DOI: 10.1016/j.jtos.2025.06.001
Barry Power , Michael T.M. Wang , Ally L. Xue , Jennifer P. Craig
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引用次数: 0
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Ocular Surface
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